Maintaining the integrity of the anatomic components of the eye facilitates the delicate manipulations, performed within small areas, of ophthalmological surgery.
One component which may be controlled is the anterior chamber of the eye. As shown in FIG. 1, the anterior chamber is located between the cornea and the iris. Just posterior to the iris is the lens, which is interposed between the anterior chamber and the larger vitreous chamber, filled with vitreous humor. Maintaining the structural integrity of the anterior chamber minimizes the risk that the endothelium and/or the iris will be damaged during surgery. The introduction of viscoelastic materials, such as sodium hyaluronate, chondroitin sulfate, hydroxypropyl methylcellulose, and methylcellulose, into the anterior chamber prevents the chamber from collapsing during surgery.
Another component that may be controlled is pupil size. During cataract surgery, it is desirable that the pupil is dilated, so that access to the lens is simplified and the insertion of a posterior chamber implant is facilitated. A variety of mydriatic drugs, such as atropine (a cholinergic blocker), phenylephrine (an adrenergic stimulator), and prostaglandin inhibitors have been used in this regard, and have hitherto predominantly been administered via external application.
Conversely, in refractive implants and secondary aphakic implants, a smaller ("miotic") pupil is desirable, in order to reduce iris trauma, avoid anterior synechias, prevent iris tucking, and facilitate appropriate positioning of the implant. Externally applied pilocarpine and carbachol (cholinergic stimulators), and physostigmine, demecarium bromide, echothiophate iodide, and isoflurophate (cholinesterase inhibitors) have been used for this purpose.
During surgery, however, and in the open eye, the efficacy of topical medication is reduced. Dilution and runoff preclude a continued high dose of effective medication. Even the direct introduction of miotic agents such as acetylcholine chloride or carbachol do not provide long term effects and often require frequent repeated administration into the open eye.
Previous attempts to achieve long-term maintenance of effective drug levels have employed sustained drug delivery technology, using systemic or transdermal administration, or the positioning of a bioerodible drug delivery device external to the eye. Such methods have been used primarily to control intraocular pressure in glaucoma patients. However, prior to the present invention, no method has been devised which combines sustained mydriatic or miotic drug delivery with maintenance of the structural integrity of the anterior chamber.
Local anesthesia has been the mainstay of ocular surgery. Topical agents have been employed to anesthetize the cornea and conjunctiva, and infiltrative anesthesia has been used to create sensory anesthesia and motor akinesia necessary for eye surgery. When injected into the muscle cone, these agents anesthetize the ciliary ganglion, afferent nerves and the motor innervation to the extra-ocular muscles. However, retrobulbar hemorrhage, caused by muscular or vascular trauma, is a potential complication of this form of anesthesia which may preclude performing the surgical procedure. More rarely, perforation of the globe, optic nerve damage, and even total visual loss can occur. Further, systemic absorption of anesthetic may cause seizures, respiratory problems, and even death.
To avoid these potential complications, infiltration anesthesia has been carried out with subtenons injections, subconjunctival injections and direct infiltration of one or more extra-ocular muscles. This approach, while somewhat more cumbersome, has reduced the potential anesthetic-related complications, but carries its own risks, such as chemosis, subconjunctival or subtenons hemorrhage and incomplete sensory and motor anesthesia, particularly during ciliary body and iris manipulation.
With the advent of extracapsular cataract surgery as a primary approach, a different set of anesthesia requirements has evolved. The need for motor anesthesia has been reduced, as instrumentation utilized during the surgical procedure may be used to fixate the globe. The need for bridle sutures, whose placement can be painful, has been virtually eliminated. What remains is the requirement to prevent pain, particularly that induced by iris manipulation. Intracameral anesthetics directly placed into the anterior chamber have been used in this context.
The use of intracameral anesthetic may be effective, but may require frequent instillation of anesthetic, particularly at times when the surgeon is involved in other steps and may not be able to add additional material with safety. Further, conventional anesthetic solutions typically exit the eye promptly, through the surgical site, through normal outflow channels, and through iris and ciliary body surfaces.
What would be desirable is a sustained release system which maintains anesthetic presence and simultaneously reduces the surge effect of intracameral placement and immediate loss through the aforementioned pathways. What would be further desired is a drug delivery system that achieves duration of anesthetic release, a more uniform release of the anesthetic over time, and control of osmotic pressure associated with the equilibrium formed between the ions of the anesthetic and the existing ions in the eye fluids.